CN107209174B

CN107209174B - System and method for determining electrochemical hematocrit by alternating current impedance phase angle detection

Info

Publication number: CN107209174B
Application number: CN201580074371.7A
Authority: CN
Inventors: G·L·休斯; R·D·杰斯温恩
Original assignee: Polymer Technology Systems Inc
Current assignee: Polymer Technology Systems Inc
Priority date: 2014-11-25
Filing date: 2015-11-25
Publication date: 2020-01-21
Anticipated expiration: 2035-11-25
Also published as: US20230273144A1; MX2017006831A; EP3224620A4; US20160146750A1; US11680925B2; EP3224620A1; WO2016086148A1; CN107209174A

Abstract

A system for determining hematocrit levels includes a test strip configured to receive a sample; a meter configured to accept a test strip; and further includes circuitry and a microprocessor configured to apply electrical energy to the test strip and the sample and determine an electrical property of the sample, an impedance phase angle or impedance magnitude of the test strip and the sample, and calculate a hematocrit level of the sample based on the electrical property.

Description

System and method for determining electrochemical hematocrit by alternating current impedance phase angle detection

Background

Hematocrit is a blood test that measures the volume percentage of whole blood that consists of red blood cells. This measure depends on the number of erythrocytes and on the size of the erythrocytes. Hematocrit (Ht or HcT, english spelling "haematacryl") is also known as "hematocrit" (PCV) or "red blood cell volume fraction" (EVF). Normally, men are about 45% and women are about 40%.

In many cases, it is desirable to know the percentage of red blood cells in an individual's blood. Hematocrit levels can indicate excessive blood loss (including internal bleeding), destruction of red blood cells (due to disease), reduced erythropoiesis, malnutrition problems, excessive moisture, dehydration, low oxygen availability, polycythemia, pulmonary heart disease, and other conditions. Hematocrit levels can also affect the results of various blood analyte tests.

Disclosure of Invention

In one embodiment, a system for determining a level of hematocrit includes a test strip configured to receive a sample and a meter configured to receive the test strip; and further includes circuitry and a microprocessor configured to apply electrical energy to the test strip and the sample and determine an impedance magnitude and phase angle of the test strip and the sample, and calculate a hematocrit level in the sample based on the impedance magnitude and phase angle. Optionally, the circuitry and microprocessor are further configured to determine the magnitude and phase angle of the impedance of the test strip and sample. Alternatively, the hematocrit level is based on the impedance phase angle and the impedance magnitude. In one configuration, the circuitry and microprocessor are further configured to determine a glucose level of the sample. In another configuration, the measured hematocrit level is based on a correlation between the impedance magnitude and the phase angle, wherein the glucose level and the hematocrit level have different but proportional effects on the impedance magnitude and the impedance phase angle such that each of the glucose level and the hematocrit level is measurable. Optionally, the test strip includes a first sample window including a first electrode and a second electrode. Alternatively, both glucose and hematocrit levels are measured from samples in a single sample window. Optionally, the single sample window comprises a first set of electrodes and a second set of electrodes. In another configuration, the first set of electrodes is configured to detect an impedance magnitude and the second set of electrodes is configured to detect an impedance phase angle. Optionally, the test strip includes a first sample window and a second sample window, the first sample window including electrodes having reagents for glucose detection.

In one embodiment, a method for determining a level of hematocrit includes providing a system including a test strip configured to receive a sample; a meter configured to accept a test strip, and further comprising circuitry and a microprocessor configured to apply electrical energy to the test strip and the sample and determine an impedance magnitude and phase angle of the test strip. The method also includes receiving a sample at the test strip and inserting the test strip into the meter. The method further includes applying a current from the meter to a test strip. The method further comprises determining the phase angle of the sample with the circuit and microprocessor. The method further includes calculating a hematocrit level of the sample at the meter and providing an output of the hematocrit level to a user. Optionally, the method further comprises determining the impedance of the test strip and the sample with the circuit and microprocessor. In one configuration, the hematocrit level is based on the impedance phase angle and the impedance magnitude. Optionally, the method further comprises determining the glucose level of the sample with the circuit and the microprocessor. Optionally, the measured hematocrit level is based on a correlation between the impedance magnitude and the phase angle, wherein the glucose level and the hematocrit level have different but proportional effects on the impedance magnitude and the impedance phase angle such that each of the glucose level and the hematocrit level is measurable. Alternatively, the test strip includes a first sample window including a first electrode and a second electrode. In one configuration, both glucose and hematocrit levels are measured from samples in a single sample window. In another configuration, the single sample window includes a first set of electrodes and a second set of electrodes. Optionally, the first set of electrodes is configured to detect an impedance magnitude and the second set of electrodes is configured to detect an impedance phase angle. Alternatively, the test strip includes a first sample window and a second sample window, the first sample window including electrodes having reagents for glucose detection.

In one embodiment, a system for determining hematocrit levels includes a test strip configured to receive a sample; a meter configured to accept a test strip. The system also includes circuitry and a microprocessor configured to apply electrical energy to the test strip and the sample and determine one of the electrical properties of the sample, the magnitude of the impedance or the phase angle, and calculate the hematocrit level of the sample based on the at least one electrical property.

Brief description of the drawings

FIG. 1 shows exemplary test results using an electrochemical test strip and meter to detect glucose;

FIG. 2 depicts exemplary results showing that phase shift is related to hematocrit and glucose levels;

FIG. 3 depicts exemplary results showing that for a variety of different glucose levels, the impedance increases when the hematocrit level is higher;

FIG. 4 illustrates an exemplary conceptual model of how hematocrit may change the magnitude of impedance;

FIG. 5 illustrates an exemplary conceptual model of how hematocrit changes the impedance phase angle;

fig. 6 depicts exemplary results showing a graph of impedance vs. time for different hematocrit levels in a 9mV-lkHz X301 test strip.

FIG. 7 depicts exemplary results showing that a phase angle metric provides a difference in hematocrit levels; and

fig. 8 shows an exemplary configuration of a test strip and meter combination.

Detailed Description

Certain terminology is used herein for convenience only and is not to be taken as a limitation on the embodiments of the system and method for determining electrochemical hematocrit via magnitude and phase angle detection of alternating current electrical impedance. In the drawings, like reference characters are used to designate like elements throughout the several views.

Hematocrit is typically measured using a coulter counter. The output of the coulter counter is an electronic signal that can be used to automatically adjust the output of a lipid meter (lipid meter). For some health analyses, hematocrit levels may be important. The presence of hematocrit can affect the detection of glucose, various lipids, and various other analytes. Thus, in many experiments, hematocrit is removed or compensated.

FIG. 1 shows exemplary test results using an electrochemical test strip and meter for detecting glucose. The samples provided have different hematocrit levels, thereby enabling the measurement of the hematocrit effect on glucose. FIG. 1 shows that at different hematocrit levels, the same glucose level produces different impedance readings. This study was conducted with alternating current. The x-axis represents time and the y-axis represents impedance. Hematocrit levels of 20%, 45%, and 70% are shown by the different lines.

Fig. 2 shows that the phase shift is related to hematocrit and glucose level. Thus, if the glucose level of the sample is determined, the hematocrit level may be determined from the phase shift. At various glucose levels, an increase in hematocrit results in a decrease in phase shift.

FIG. 3 shows that for a variety of different glucose levels, the impedance increases as the hematocrit level is higher. Again, this represents the test done on the test strip with the electrochemical meter. An increase in hematocrit results in an increase in the magnitude of the impedance measured.

From the fig. 1-3, it can be determined that hematocrit level affects the measured impedance and phase angle because it relates to glucose detection and the phase shift is related to glucose level and hematocrit level; however, when comparing the phase shift to the red blood cell specific volume level, the phase shifts of different glucose levels have approximately the same slope. Thus, it is possible to determine the hematocrit level based on the impedance level and the phase shift level.

FIG. 4 shows an exemplary conceptual model of how hematocrit may change the magnitude of impedance. As shown, is the magnitude of the impedance over a 10 second period versus some percent hematocrit. The slope may be obtained from a data determination equation. In this case, the equation is 18.154x + 3740.2. This is purely exemplary of a working equation, and a variety of other equations are possible. This impedance magnitude, vs. hematocrit plot replicates the expected and previously observed results.

FIG. 5 shows an exemplary conceptual model of how hematocrit changes the impedance phase angle. As shown, is the magnitude of the impedance over a 10 second period versus some percent hematocrit. The slope may be obtained from a data determination equation. In this case, the equation is 0.0607x + 28.364. This is purely exemplary of a working equation, and a variety of other equations are possible. This impedance phase angle vs. hematocrit plot replicates the expected and previously observed results.

Fig. 6 shows a graph of impedance vs. time for different hematocrit levels in a 9mV-lkHz X301 test strip. The hematocrit levels of these samples were unknown; however, hematocrit levels can be determined from impedance readings at approximately 5.783 seconds, 7.763 seconds, and 10.734 seconds. The significance of this figure is to help determine when the effect of hematocrit is constant. In this figure, the y-axis may represent the impedance magnitude. As shown, after about 10 seconds, the hematocrit effect on the impedance levels flat enough to provide a measurable difference between the various hematocrit levels depending on the impedance (magnitude and phase angle).

Experimentally, test strips with unknown hematocrit levels are tested to determine whether the test strips can be distinguished by impedance (magnitude and phase angle). As shown in FIG. 7, the phase angle metric helps distinguish hematocrit levels.

Thus, multiple arrangements are possible for the test strip. In one version, an electrochemical test strip may be provided, as well as a meter for reading the test strip. The electrochemical test strip includes a first electrode and a second electrode to measure the impedance and phase change provided by the sample. The meter is designed to supply current to the test strip and monitor the current to determine impedance and phase change.

In many embodiments, the meter includes a calibration algorithm for calculating hematocrit. Alternatively, the algorithm may be implemented in a variety of devices. Various embodiments of the systems and methods described herein may be implemented in whole or in part in software and/or firmware. Such software and/or firmware may take the form of instructions contained in or on non-transitory computer-readable storage media. Which may be subsequently read or executed by one or more processors to enable the operations described herein. The instructions may take any suitable form, such as but not limited to source code, compiled code, interpreted code, executable code, static code, dynamic code, and the like. Such computer-readable media may include any tangible, non-transitory medium that stores information in one or more computer-readable forms, such as, but not limited to, Read Only Memory (ROM), Random Access Memory (RAM), magnetic disk storage media, optical storage media, flash memory, and the like.

Embodiments of the systems and methods described herein can be implemented in a variety of systems, including but not limited to smartphones, tablets, laptops, and combinations of computing devices and cloud computing resources. For example, some operations may occur in one device and other operations may occur at a remote location, such as one or more remote servers. For example, data collection may be performed in a smartphone and data analysis may be performed in a server or cloud computing resource. Any single computing device or combination of computing devices can perform the methods described herein.

The microprocessor in the meter then estimates the hematocrit level according to the internal equation. In some alternatives, the test strip may further include another test zone with additional electrodes or reactants that react with the glucose. In some alternatives, the glucose test zone may be the same as the hematocrit test zone. Since the amount of glucose in the sample affects the ratio of impedance and phase angle differently than hematocrit, glucose levels and hematocrit levels can be determined. In the above configuration, additional test zones may also be included. These additional test zones are capable of detecting a variety of hematocrit-corrected analytes.

An exemplary configuration of a test strip and meter combination is shown in fig. 8. Basically, test strip 810 is configured with a working electrode 812 and a counter electrode 811. In the alternative, additional electrodes, such as reference electrodes and the like, may be incorporated. Test strip 810 also includes connection points 820, 821. The connection points 820, 821 are configured to contact the connection points 831, 832 on the meter circuit 830 when the test strip 810 is inserted into the meter. The meter circuit 830 may include a firing buffer amplifier loop 840, a transimpedance amplifier 850, and a switch matrix 860. The excitation buffer amplifier loop 840 may provide the desired excitation current to the test strip 810 via the switch matrix 860. Typically, the pump buffer amplifier loop 840 provides the required current to make the measurement. Transimpedance amplifier 850 is interconnected with the microprocessor and generally accepts current through test strip 810, including the sample, and provides a signal in a usable form to the microprocessor. The transimpedance amplifier 850 provides current-to-voltage conversion for measurement by ADC (microprocessor).

The system shown in fig. 8 is merely exemplary and numerous alternatives are available.

Briefly, the idea is to determine the hematocrit of a sample by reading the AC impedance at the beginning, middle or end of a DC measurement. The hematocrit value can be assigned from a predetermined equation by determining the magnitude, phase angle, or both. After determining the hematocrit, the concentration can be adjusted mathematically based on known deviations of the hematocrit effect.

Red blood cell interference has been identified as a factor in the analysis results that causes bias in many analyte systems, including those testing for glucose and cholesterol analytes. The ability to determine the effect of hematocrit on the measurement of analyte on a meter can greatly reduce the error in analyte results. A dedicated microprocessor chip can be used to detect glucose analytes in a whole blood sample via DC measurements, as well as to apply AC voltages to the electrodes. From the real and assumed results, the magnitude and phase angle are calculated. System-specific factors such as hematocrit correction factors (linear regression parameters or single coefficients), time scales for which the AC and DC voltages are applicable, and the use of the phase angle and/or magnitude results can determine a "corrected" glucose value from the DC measurements.

While specific embodiments have been described in detail in the foregoing detailed description and illustrated in the accompanying drawings, it will be appreciated by those skilled in the art that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure and its broad inventive concept. It is understood, therefore, that the scope of this disclosure is not limited to the particular examples and implementations disclosed herein, but is intended to cover modifications within the spirit and scope thereof as defined by the appended claims, and any and all equivalents thereof.

Claims

1. A system for determining hematocrit levels, the system comprising:

a test strip configured to receive a sample;

a meter configured to accept a test strip; and

further included is a circuit and microprocessor configured to apply power to and determine an impedance phase angle of the test strip and the sample, the circuit and microprocessor further configured to determine an impedance magnitude of the test strip, and based on the impedance phase angle and the impedance magnitude, calculate a level of hematocrit in the sample based on glucose and hematocrit affecting the impedance phase angle and the impedance magnitude at different rates.

2. The system of claim 1, wherein the circuitry and microprocessor are further configured to determine a glucose level of the sample.

3. The system of claim 2, wherein the measured hematocrit level is based on a correlation between the impedance magnitude and the phase angle, wherein the glucose level and the hematocrit level have different but proportional effects on the impedance magnitude and the impedance phase angle such that each of the glucose level and the hematocrit level is measurable.

4. The system of claim 3, wherein the test strip includes a first sample window including a first electrode and a second electrode.

5. The system of claim 4, wherein the glucose level and hematocrit level are both determined from samples in a single sample window.

6. The system of claim 5, wherein the single sample window comprises a first set of electrodes and a second set of electrodes.

7. The system of claim 6, wherein the first set of electrodes is configured to detect an impedance magnitude and the second set of electrodes is configured to detect an impedance phase angle.

8. The system of claim 4, wherein the test strip includes a first sample window and a second sample window, the first sample window including electrodes having reagents for glucose detection.